Oxidative stress is implicated in the etilogy of age- related macular degeneration, retinopathy of prematurity, and diabetic retinopathy. In our attempt to understand the mechanism(s) of oxidative damage to the retina, we have investigated the expression of heme oxygenase (HO-1, HSP32) in the retina and retinal pigment epithelium (RPE) in response to oxidative stress. Stress agents such as metal ions (cadmium, mercury, and cobalt), menadione, sodium arsenite, heme, and iodoacetamide greatly increased the expression of HO-1 protein and mRNA in RPE cells in culture. The expression of HO-1 in these cells was found to be regulated by transforming growth factor-beta (TGF-beta) but not by any other growth factor tested. The interaction of light with visual pigments could produce reactive oxygen species injurious to the retina. The effect of intense visible light on the expression of HO-1 was investigated in a rat model system. Retinal samples from animals exposed to bright light exhibited an unusually high amount of HO-1 protein and mRNA compared with controls. Importantly, treatment of rats with dimethylthiourea, an antioxidant, before light exposure effectively blocks the increase in HO-1 mRNA. This gives evidence in favor of the theory that light damage is transduced through an oxidative pathway and also points toward possible protective modalities in the future.